tbuckley/cabot-search huggingface dataset:
Prognostic value of the SEER-Medicare myelodysplastic syndromes risk score for a contemporary cohort of patients with MDS.
Authors: Amber Afzal, Mark A. Fiala, Meagan Jacoby, Matthew Walter
Journal: Journal of Clinical Oncology (2022)

e18762 Background: Prognostication of patients with myelodysplastic syndromes (MDS) using IPSS-R is not possible in administrative database analysis. In 2014, a claims-based prognostic scoring system, the SEER-Medicare MDS Risk Score (SMMRS) was developed to risk-stratify MDS patients for overall survival using ICD9 codes {Uno, 2014}. In 2015, ICD9 codes were replaced by ICD10 codes. In this study, we updated SMMRS with inclusion of both ICD-9 and -10 codes, and studied its predictive value for overall survival, leukemia-free survival and initiation of treatment among MDS patients. Methods: Patients with MDS were identified through ICD-O-03 codes in the SEER-Medicare database between 2007 and 2017. SMMRS was calculated using MDS subtype, age, comorbidities, cytopenias, transfusion-dependence, and recent hospital admissions. We analyzed the association of SMMRS with overall survival, leukemia-free survival (time from MDS diagnosis to leukemia), and initiation of treatment (hypomethylating agents /stem cell transplant) in Cox proportional hazards models while adjusting for potential confounders. Results: Patients with MDS (N = 12,710) had a median age of 80 years, half were males, and most were Caucasians. SMMRS stratified patients into low-risk (n = 3155), intermediate-1 risk (n = 3255), intermediate-2 risk (n = 3121), and-high risk (n = 3209) categories at diagnosis. The overall survival, leukemia-free survival and treatment initiation for patients in each SMMRS category is summarized in Table. The 5-year overall survival for the entire cohort was 20%. At 5 years, 10% of the MDS patients had transformed to leukemia, and 1/3rd had started MDS treatment. Conclusions: SMMRS based on ICD-9 and -10 codes predicts overall survival, leukemia-free survival and MDS treatment initiation by stratifying MDS patients into 4 risk-categories. It can be utilized to design/analyze future observational studies.[Table: see text]
Cytoreductive surgery plus HIPEC for advanced epithelial ovarian cancer: Analysis from a multicentric national Indian HIPEC registry of 1,470 patients—An ISPSM Collaborative study.
Authors: S.P. Somashekhar, S.V.S. Deo, Rupinder Sekhon, Subramanyeshwar Rao Thammineedi, Harit Chaturvedi, Ganesh M S, Rama Joshi, Kalpana Kothari, Amit Gandhi, Ashwin K. Rajgopal, M D Ray, R Rajagopalan Iyer, Hemanth G N, Rohit Kumar
Journal: Journal of Clinical Oncology (2022)

5525 Background: Improved long-term results can be achieved in advanced epithelial ovarian cancer (EOC) patients using optimal cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: Indian society of peritoneal surface malignancy (ISPSM) is a registered body which maintains prospective data of 26 centers across India who perform CRS –HIPEC. From February 2017 until January 2022, 1470 patients with advanced EOC were treated with CRS-HIPEC. He general practice patterns and the oncological outcomes in terms of progression free survival (PFS) and overall survival (OS) &amp; post-operative morbidity and mortality is reported. Results: Upfront (n = 156), interval (n = 645) and recurrent (n = 669) cytoreductions were performed based on the timeline at presentation. Mean age 54.5±10.74, PCI 13. 6±5.2, duration of surgery 10.6±1.h hrs. 36.4% had total peritonectomy, 12.7% had multivisceral resection, 41.8%had bowel resections and stoma rate was 7.4%. 60.3% had semiopen HIPEC, 83.1% used cisplatin for HIPEC and 83.1 % had HIPEC for 90 minutes. Overall G3-G5 morbidity was 25.4% with major ones being post-operative intra-abdominal collection (21.8%), electrolyte imbalance (16.4%), pulmonary (16.4%) followed by hematological (12.7%). Surgical morbidity was more in upfront cytoreduction group compared to interval group (20% versus 13.5%) and recurrent group (20% versus 15%), respectively. The 30 day mortality was 3.8%. With a median follow-up of 46 months, median PFS was 33 months in primary (upfront plus interval) group and 16 months in recurrent cytoreduction group. Median OS was not achieved in both primary and recurrent groups (4 year OS rates: 60 and 55%, respectively). Conclusions: This prospective database provides a collation and audit of the management of advanced epithelial ovarian cancer with CRS HIPEC in multiple centers registered under ISPSM. In advanced EOC patients, CRS plus HIPEC offers potential benefits in PFS and OS rates, with acceptable rates of morbidity and mortality and can be practiced even in resource constrained setting.
Clinical application of precision medicine among oncologists: A case study in <i>RET-</i>targeted therapy.
Authors: Krista Marcello, Marcia S. Brose, Taofeek K. Owonikoko, Karen L. Reckamp, Laura J. Tafe, Rachael Andrie, Kevin Obholz
Journal: Journal of Clinical Oncology (2022)

e18705 Background: Precision medicine has revolutionized cancer care across multiple tumor types and new actionable biomarkers and targeted therapies are emerging at an unprecedented pace, creating myriad opportunities to optimize care and mitigate the often-dire sequelae of traditional cancer therapy. Many oncology healthcare professionals (HCPs) in practice are not employing optimal testing methodologies to detect biomarkers in patients who could benefit from novel targeted therapies. In this study, we analyze HCP awareness and application of RET alteration testing and integration of recently approved, new-generation selective RET inhibitors into practice for appropriate patients with NSCLC and thyroid cancer. Methods: In August 2020 HCPs were surveyed on RET alteration testing and use of RET-targeted therapeutics in their current practice. Study eligibility criteria included active HCPs in an oncology, pulmonology, or pathology practice. A curriculum of live and online educational activities was then developed for any interested oncologists and pathologists on RET alteration testing and/or targeted therapy for RET-altered lung and thyroid cancers. These activities included case studies, polling, and evaluations that provided additional insight on self-identified practice trends. In June 2021, at the completion of the educational program, eligible HCPs were surveyed again on RET alteration testing and selection of RET inhibitor therapy for appropriate patients. Results: In August 2020, 123 practicing HCPs completed the initial survey and 33% were testing patients for RET gene alterations and 18% were aware of the most sensitive testing assay for detection of RET fusions. 25% and 7%, respectively, were aware of the current indications for RET inhibitors in RET fusion–positive NSCLC and RET-altered thyroid cancer. Self-identified practice trends identified among the unselected cohort of 12,537 individual HPCs participating in the educational activities also demonstrated similar lack of appropriate testing for RET alterations and use of RET inhibitors. In June 2021, 60 practicing HCPs completed the follow-up survey and 40% were testing patients for RET gene alterations and 25% were aware of the most sensitive testing assay for detection of RET fusions. 52% and 22%, respectively, were aware of the current indications for RET inhibitors in RET fusion–positive NSCLC and RET-altered thyroid cancer. Conclusions: The rate of broad testing for RET alterations across patients with NSCLC and thyroid cancer remains low and many HCPs lack understanding of when to consider treating with a RET inhibitor. These results underscore the lag in adoption of optimal precision medicine approaches in oncology and the need for expert guidance and educational activities to optimize individualized, biomarker-driven treatment approaches for patients with cancer.
Human papillomavirus DNA resides in surgical drain fluid exosomes from HPV+ oropharyngeal squamous cell carcinoma patients and can be spread to neighboring HPV-negative cells.
Authors: Zhongping Xu, Noah Earland, Peter K. Harris, Sophie P. Gerndt, Ricardo J. Ramirez, Andrew I. Hearn, Nicholas P. Semenkovich, Aadel A Chaudhuri, Jose P. Zevallos
Journal: Journal of Clinical Oncology (2022)

e18050 Background: Human papillomavirus (HPV) is the primary driver of oropharyngeal squamous cell carcinoma (OPC) in the US. Previous studies have investigated the role of plasma and saliva-based cell-free HPV DNA in OPC, yet the pathophysiological impact of exosomes in HPV+ OPC remains unknown. Exosomes are nanometer-sized membrane vesicles of endocytic origin carrying DNA, RNA and proteins, and have been shown to exist in blood, plasma, and in urine. We hypothesize that serosanguinous fluid drained from the postoperative bed, which we call “surgical drain fluid” (SDF) also contains exosomes. We further hypothesize that exosomes derived from SDF in HPV+ OPC patients contain HPV DNA that can be directly transmitted into HPV-negative cells. Methods: Twenty-six 5-mL SDF samples were collected following surgical neck dissections directly from the surgical drain; 21 from HPV+ and 5 from HPV- OPC patients. Exosomes were isolated from SDF using the Qiagen exoEasy kit. Exosome structure was characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Western blotting (WB) targeted known exosomal surface markers. Exosomes were pretreated with DNase (New England Biolabs) to cleave the surface DNA, then exosomal DNA was extracted using a cell-free DNA isolation kit (Sigma). TaqMan real-time PCR was employed to detect HPV16 copy numbers. Lastly, exosomes isolated from 3 HPV+ patients’ SDF and 1 HPV- patient’s SDF were incubated with HPV- cell lines, SCC22A and SCC25, in order to query exosome-mediated HPV transmission. Results: TEM identified exosomes as round/oval-shaped vesicles measuring between 70 and 150 nm. NTA enumerated an average of 1.5 x 10 11 particles per mL of SDF. WB further confirmed exosomal identity with strong CD63, CD9, and TSG101 signal detected. Among SDF exosomes from HPV+ OPC, 81% (n = 17) had detectable HPV16 DNA by real-time PCR, while all HPV- SDF exosomes (n = 5) showed undetectable HPV16. Paired comparison of HPV16 levels within exosomes to total HPV16 in SDF revealed an average of 90% of HPV16 in SDF was contained within exosomes. In an in vitro assay, SCC22A and SCC25 cells treated with HPV16 + exosomes became real-time PCR-positive for HPV16, while cells treated with HPV16- exosomes remained HPV16 negative. Conclusions: This study demonstrates that SDF, a novel post-surgical biofluid analyte, is enriched for HPV-containing exosomes in HPV+ OPC patients. We also found that exosomes from HPV+ OPC patients can transmit HPV to HPV-negative cells, suggesting a novel mode of virus-mediated spread of disease.
Increased incidence of immune-mediated myocarditis in advanced skin malignancies treated with immune checkpoint inhibitors in the COVID-19 era.
Authors: Allison Gradone, Vincent T Ma, Leslie Anne Fecher, Sarah Elizabeth Yentz, Alexi Vasbinder, Salim S. Hayek, Christopher D. Lao
Journal: Journal of Clinical Oncology (2022)

2664 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced stage skin malignancies. Immunotherapy related adverse events (irAE) are toxicities associated with ICI therapy. Myocarditis is a rare life-threatening irAE. We attempt to characterize cases of myocarditis related to ICI therapy that have occurred since the start of the COVID-19 pandemic. Methods: We performed a single-center, retrospective cohort analysis of patients with advanced stage skin cancers who were treated with ICIs and identified cases of ICI-mediated myocarditis. ICI-mediated myocarditis was defined as evidence of myocardial injury in the setting of irAEs and exclusion of cardiovascular causes. Clinicopathologic variables and clinical outcomes were assessed in these patients. Results:A review of 361 patients that received ICI from 9/2014 – 10/2019 found 0 cases of ICI-mediated myocarditis. From 11/2019 – 12/2021, an additional 425 patients were identified of whom 11 (2.6%) developed ICI-mediated myocarditis. 10 patients had melanoma and 1 patient had Merkel cell carcinoma. 10/11 patients were male. 9/11 were treated with anti-PD-1 monotherapy and 2/11 were treated with ipilimumab with nivolumab. All patients had elevated high sensitivity troponin (median 361 pg/mL on presentation, reference range 0-19 pg/mL). 11/11 patients presented with elevated CPK (median 1734 IU/L, reference range 38-240 IU/L) and 8/11 presented with elevated AST:ALT ratio (median 1.58:1) on routine screening which prompted further investigation. 1 patient tested positive for COVID-19 13 days after initial biochemical concern for myocarditis, and 5 patients had received COVID-19 vaccines between 2.5-11 months prior to myocarditis onset. All patients were treated with high dose steroids, and 4 were treated with abatacept. 2 patients died within 30 days after diagnosis of myocarditis and 2 patients later died from malignancy progression. 2 patients developed progressive disease and 1 was successfully rechallenged with ICI with no myocarditis recurrence. 2 patients remain on active surveillance, 2 continue on a steroid taper, and 1 was lost to follow up. All patients with at least 5 months of follow up from myocarditis onset (n = 5) had persistently elevated HS-troponin despite normalization of CPK levels. Conclusions: In this single center study, we noted an increase in the frequency of ICI-mediated myocarditis in patients with advanced skin cancers during the pandemic era (2.6% vs 0% pre-pandemic) which is higher than reported in the literature (0.04-1.14%). The impact of COVID-19 during this time is suspicious and warrants further investigation. Therefore, we suggest heightened awareness in the COVID-19 era that elevated CPK levels and AST:ALT ratios merits further diagnostic investigation of ICI-mediated myocarditis.
HGG-31. Unique case of a bithalamic H3K27-wildtype diffuse midline glioma, EGFR-altered with methylated MGMT
Authors: James Reinecke, Catherine Cottrell, Sarah Rush, Alexis Judd, Joshua Palmer, Christopher Pierson, Margot Lazow, Yelena Wilson
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Diffuse midline gliomas are aggressive pediatric brain tumors frequently associated with somatic mutations in histone genes H3F3A (H3.3) and HIST1H3B (H3.1), which promote gliomagenesis through reprograming of the epigenetic landscape by inhibiting the tri-methylation of H3K27 (H3K27-me3). H3K27M-mutant gliomas comprise over 80% of diffuse midline gliomas, and are characterized by dismal outcomes as well as near-ubiquitous absence of MGMT promoter methylation. The subset of H3K27-wildtype diffuse midline gliomas remains incompletely understood with regards to underlying pathogenesis, therapeutic targets, and prognosis. We present the clinical, imaging, histopathologic, and molecular characteristics of a pediatric patient with a bithalamic H3K27-wildtype diffuse midline glioma, EGFR-altered with methylated MGMT. CASE: A 10-year-old female presented with an infiltrative bithalamic T2-hyperintense mass lacking diffusion restriction or contrast enhancement on MRI. Initial pathological inspection from biopsy was consistent with high-grade neuroepithelial tumor favoring high-grade glioma, however, immunohistochemistry was negative for H3K27M and demonstrated reduced H3K27-me3. DNA sequencing uncovered mutations in EGFR (exon 20 insertion) and TP53 (R175H), with overexpression of EGFR and CDK6 (but not EZHIP) identified by RNA-sequencing. Methylation profiling was consistent with high-grade glioma, matching closest with glioblastoma, IDH-wildtype, with positive MGMT promoter methylation. Treatment was initiated with focal chemoradiotherapy with concurrent temozolomide, with plans for adjuvant temozolomide/ lomustine.DISCUSSION: Our case adds to growing evidence suggesting bithalamic tumors represent a distinct genetic and epigenetic subset of diffuse midline gliomas often defined by H3K27-wildtype status, loss of H3K27-me3, and EGFR receptor alterations. Our patient’s H3K27-wildtype, EGFR-altered tumor had reduced H3K27-me3 as well as positive MGMT promoter methylation, a molecular characteristic that has not been well-studied in H3K27-wildtype bithalamic gliomas, but is suspected to confer sensitivity to alkylating chemotherapy. The prevalence, prognostic impact, and therapeutic implications of MGMT promoter methylation in bithalamic H3K27-wildtype diffuse midline gliomas, including potential association with EGFR aberrations, requires further exploration.
#SurgOnc: Global discussions about surgical cancer care on Twitter during COVID-19.
Authors: Sofia Gereta, Vishal R. Patel, Michael Mackert, Alex Bernard Haynes
Journal: Journal of Clinical Oncology (2022)

11045 Background: Social media platforms such as Twitter are highly utilized to communicate about cancer care. Although surgery is the primary treatment for solid malignancies, little is known about public perceptions or communication behaviors regarding this treatment modality. Further, prolonged lockdowns and widespread delays of planned operations during the COVID-19 pandemic have magnified the importance of virtual communication about surgical cancer care. Methods: Tweets referencing cancer surgery were collected from January 2018 to January 2022 using Twitter’s Application Programming Interface. Account metadata was used to predict user demographic information and to compare tweeting metrics across users. Natural language processing models were applied to tweet content to resolve common topics of conversation and to classify tweets by cancer type. Results: There were 442,840 original tweets about cancer surgery by 262,168 users. Individuals accounted for most users (65%) while influencers accounted for the least (1.4%). Influencers made the most median impressions (19,139). Of 240,713 tweets discussing surgery for specific cancers, breast (20%) and neurologic (17%) cancers were most mentioned. When adjusting for national rates of procedures performed, tweets about surgery for neurologic cancers were the most common (231 tweets per 1000 procedures) whereas those for urologic cancers were the least common (15 tweets per 1000 procedures). Discussions about cancer surgery research made up 31% of tweets before the pandemic but only 11% of tweets during the pandemic. During the pandemic, concern regarding COVID-19 related delays was the most tweeted topic (23%). Cancer surgery research was most cited by oncologists, as well as in tweets about hepatopancreatobiliary and colorectal cancers. The cost of surgery was commonly mentioned in tweets about breast and gynecologic cancers and contained the most negative sentiment score (-0.7). Conclusions: Twitter was highly utilized to discuss surgical cancer care during the COVID-19 pandemic. During the pandemic, conversations shifted focus from research to survivorship and reflected real-time events such as COVID-19-related surgical delays. We identified the financial burden of cancer care as a commonly held concern among patients discussing cancer surgery on social media. Future public health outreach about cancer surgery may be optimized by coordinating with influencers and by targeting topics of concern like cost of surgery and undermentioned content like urologic cancers. Twitter’s role as a platform for research dissemination was disrupted by the COVID-19 pandemic, and further tracking is needed regarding online research discussions after the pandemic.
KEYNOTE-365 cohort D: Pembrolizumab (pembro) plus abiraterone acetate (abi) and prednisone in chemotherapy (chemo)–naive patients with metastatic castration-resistant prostate cancer (mCRPC)
Authors: T. Todenhöfer, J.M. Piulats, C. Ferrario, M.D. Linch, M. Stoeckle, B. Laguerre, J.A. Arranz, P.C.C. Fong, W.R. Berry, U. Emmenegger, L. Mourey, N. Mar, L.J. Appleman, A.M. Joshua, H.J. Conter, X.T. Li, C. Schloss, C.H. Poehlein, J.S. De Bono, E.Y. Yu
Journal: European Urology (2022)
An Optimally Fabricated Platform Guides Cancer‐Specific Activation of Chemotherapeutic Drugs and Toxicity‐Free Cancer Treatment
Authors: Ok Jeong Moon, Chul Joo Yoon, Bo‐Ram Lee, Jeewon Lee
Journal: Advanced Healthcare Materials (2022)

Abstract Cancer chemotherapeutic drugs such as doxorubicin, mitomycin C, and gemcitabine, which are mostly small synthetic molecules, are still clinically useful for cancer treatment. However, despite considerable therapeutic efficacy, severe toxicity‐associated problems, which are mainly caused by the non‐specific mode of action such as chromosomal DNA damage and interference in the DNA replication even in normal cells, remain unresolved and a major challenge for safer and thus more widespread adoption of chemotherapy. Herein, an innovative platform is developed through beneficially integrating core peptide units into highly‐ordered, stable, and flexibly guest‐adaptable structure of apoferritin, which simultaneously fulfills high‐capacity loading of chemotherapeutic drugs compared with the case of FDA‐approved antibody‐drug conjugates, efficient drug targeting to cancer cells, and cancer cell‐specific drug release and activation. This approach dramatically reduces drug toxicity to normal cells, significantly enhances efficacy in in vivo cancer treatment without toxicity to normal organs of mice, and thus is expected to open up a novel clinical route to break through the limits of current cancer chemotherapy.
What size cutoff level should be used to implement optical polyp diagnosis?
Authors: Mahsa Taghiakbari, Heiko Pohl, Roupen Djinbachian, Joseph C. Anderson, Danny Metellus, Alan N. Barkun, Mickael Bouin, Daniel von Renteln
Journal: Endoscopy (2022)

BACKGROUND : The risk of advanced pathology increases with polyp size, as does the potential for mismanagement when optical diagnosis is used. This study aimed to evaluate the proportion of patients who would be assigned inadequate surveillance intervals when different size cutoffs are adopted for use of optical diagnosis. METHODS : In a post hoc analysis of three prospective studies, the use of optical diagnosis was evaluated for three polyp size groups: 1-3, 1-5, and 1-10 mm. The primary outcome was the proportion of patients in whom advanced adenomas were found and optical diagnosis resulted in delayed surveillance. Secondary outcomes included agreements between surveillance intervals based on high confidence optical diagnosis and pathology outcomes, reduction in histopathological examinations, and proportion of patients who could receive an immediate surveillance recommendation. RESULTS : We included 3374 patients (7291 polyps ≤ 10 mm) undergoing complete colonoscopies (median age 66.0 years, 75.2 % male, 29.6 % for screening). The percentage of patients with advanced adenomas and either 2- or 7-year delayed surveillance intervals (n = 79) was 3.8 %, 15.2 %, and 25.3 % for size cutoffs of 1-3, 1-5, and 1-10 mm polyps, respectively (P < 0.001). Surveillance interval agreements between pathology and optical diagnosis for the three groups were 97.2 %, 95.5 %, and 94.2 %, respectively. Total reductions in pathology examinations for the three groups were 33.5 %, 62.3 %, and 78.2 %, respectively. CONCLUSION : A 3-mm cutoff for clinical implementation of optical diagnosis resulted in a very low risk of delayed management of advanced neoplasia while showing high surveillance interval agreement with pathology and a one-third reduction in overall requirement for pathology examinations.